Abstract Each year there are over 2 million infections and 23,000 deaths caused by antibiotic-resistant bacteria in the United States. The World Health Organization and the Centers for Disease Control and Prevention each recently identified antibiotic resistance as one of the greatest threats to human health worldwide. Judicious antibiotic use is essential to combat the global public health crisis of antibiotic resistance and improve the health and safety of the population. A critical component in combating antibiotic resistance within the acute care setting is the antimicrobial stewardship program (ASP). ASP efforts focus on reducing unnecessary antibiotic use in hospitals and health systems and support the use of the correct agent, dose, duration, and route. The Standardized Antimicrobial Administration Ratio (SAAR), a risk-adjusted antibiotic utilization metric, has been introduced as a strategy for monitoring and comparing hospital antibiotic use. Although significant effort has gone into development of SAAR, several aspects require scientific advancement. Most importantly, there are no data to indicate if risk-adjusted antibiotic use is a good proxy for appropriate antibiotic use. If suboptimal antibiotic use metrics are used to guide stewardship strategies, ASPs may design unnecessary or ineffective interventions and, ultimately, hospitals may be inappropriately penalized in benchmarking comparisons with peer hospitals. Our long-term research goal is to support effective and evidence-based antibiotic stewardship. The objective of this project is to develop research infrastructure and collect preliminary data that will support robust assessment of antibiotic utilization metrics. To achieve our objective, we propose these specific aims: [1] evaluate the validity of one of the current risk-adjusted antibiotic use metrics by assessing correlation with the gold standard of appropriate antibiotic use and then [2] develop, test, and refine rubrics for evaluating appropriate antibiotic use in antimicrobial stewardship research studies. To achieve these aims, the proposed study will construct a retrospective cohort of inpatients admitted to Oregon Health & Science University (OHSU) hospital and Doernbecher Children?s Hospital. We will evaluate if current CDC benchmarking efforts, which focus on comparisons of risk-adjusted antibiotic use data, equate to evaluations of appropriateness of antibiotic use. To start, this work will focus on evaluating antibacterial agents predominantly used for resistant Gram-positive infections using a team of expert consultants to develop guideline driven rubrics of appropriate use. We will then employ a process of feasibility testing to refine rubrics for two additional NHSN-defined categories of high-value for stewardship programs. This includes broad-spectrum agents predominately used for both hospital-onset and community-acquired infections. Upon successful completion of this study, we will have produced the data and infrastructure necessary to perform a larger-scale, multi-site rigorous test of antibiotic utilization metrics.